# NOP56 interacts with Fibrarin to regulate the PI3K/AKT signaling pathway and inhibit apoptosis of hepatocellular carcinoma

## TL;DR

NOP56, a nucleolar protein, promotes liver cancer by interacting with fibrillarin and activating a key signaling pathway.

## Contribution

NOP56's role in HCC progression via the NOP56–FBL–PI3K/AKT/CREB axis is newly identified.

## Key findings

- NOP56 is upregulated in HCC and linked to poor prognosis.
- NOP56 knockdown reduces tumor growth and activates apoptosis in HCC cells.
- NOP56 interacts with fibrillarin to activate the PI3K/AKT/CREB pathway.

## Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. While *C-myc* is known to drive hepatocarcinogenesis, the roles of its downstream targets remain unclear. NOP56, a conserved nucleolar protein and *C-myc* target, may contribute to HCC progression.

We analyzed single-cell and bulk transcriptomic datasets to determine NOP56 expression and clinical significance. Loss-of-function assays in HCC cells, along with xenograft models, were used to evaluate its biological role. Protein interaction and pathway analyses were conducted using co-immunoprecipitation and Western blotting.

NOP56 was upregulated in malignant hepatocytes and associated with poor prognosis. NOP56 knockdown inhibited proliferation, colony formation, and migration, induced G0/G1 arrest and apoptosis, and reduced tumor growth in vivo. Mechanistically, NOP56 interacted with fibrillarin (FBL) and activated the PI3K/AKT/CREB pathway. Silencing NOP56 lowered FBL levels and suppressed pathway activity, whereas FBL overexpression partially rescued apoptotic effects.

NOP56 promotes HCC progression through the NOP56–FBL–PI3K/AKT/CREB axis. These findings reveal a previously unrecognized oncogenic role of nucleolar proteins in HCC and highlight this signaling axis as a promising therapeutic target.